Sphingolipids and Innate Immunity: A New Approach to Infection in the Post-Antibiotic Era?

Abstract

Antibiotic resistance has been demonstrated during the entire duration of antibiotic use even before medical utilization. Increasing resistance within virtually all microbes continues to be a problem. Infection with antibiotic resistant microbes has demonstrated significantly increased morbidity, death, and health-care-associated costs. Given increasing antibiotic resistance, multiple novel agents and approaches are being investigated, including antimicrobial lipids. Sphingosine and ceramide have been demonstrated to play a pivotal role in the innate immunity of the epidermis, oral mucosa, and respiratory epithelium; their role is being investigated currently in uroepithelium. Ceramide has been shown to be pivotal in the regulation of mammalian defense against Pseudomonas aeruginosa and Staphylococcus aureus pathogens commonly encountered in pneumonia. On the other hand, sphingosine appears to be equally pivotal and directly involved in pathogenic defense and has been demonstrated to "rescue" mammals from P. aeruginosa infections. Within this review, we will discuss the role of sphingolipids within innate immunity, pathogen invasion, and bacterial infection. We will discuss the antimicrobial activity of sphingosine and possibility for commercial use as an antimicrobial in the post-antibiotic era.